Differentiation between fibrin degradation products and fibrinogen degradation products by using newly developed ELISAs

We should distinguish fibrin degradation products (FbDP) from fibrinogen degradation products (FgDP) in order to analyze fibrinolysis in vivo. We analyzed some disorders associated with hyperfibrinolytic states using ELISA for FbDP, FgDP and total fibrin (ogen) degradation products (TDP) (ORGANON TEKNIKA). Each ELISA was useful in terms of reproducibility and dilution linearity of plasma samples. There was no cross-reaction between FbDP and FgDP. The FgDP/FbDP ratio in normal individuals was 1.65. In patients with DIC, it was 0.43, with FgDP level being increased. These results suggest that fibrinolysis is enhanced in patients with DIC, but it is accompanied by fibrinogenolysis. On the other hand, the FgDP/FbDP ratio in patients given urokinase (UK) was 2.88. This suggests that fibrinogenolysis is enhanced in them. In our study, the FgDP/FbDP ratio increased as DIC improved. Thus, we can regard this as an index of therapeutic effects in patients with DIC. We conclude that these three ELISA are useful in analyzing disorders associated with hyperfibrinolytic states.     

Studies on the fragments of FDP in 4 patients with DIC]

We previously studied fibrinolysis and fibrinogenolysis by analyzing fragments of fibrin/fibrinogen degradation products (FDP) employing sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. In this report, we characterized the fragments of FDP in four patients with disseminated intravascular coagulation (DIC), that were caused by various diseases. In the patients suffering from acute lymphoblastic leukemia (case 1) and acute suppurative cholangitis (case 3), DD and DY/X fragments resulting from fibrinolysis accounted for the most part of the FDP fragments. In case 3, D fragments resulting from fibrinogenolysis were also observed to much less extent. In a DIC associated with acute myeloblastic leukemia (case 2), both fibrinolysis and fibrinogenolysis were increased and resulted in high levels of D, Y and DY/X fragments, concomitant with moderate levels of DD and high molecular weight (HMW) fragments in the patient's sera. The increased fibrinogenolysis in this case was attributed to accelerated activation of plasmin. In a DIC patient of case 4, who underwent an operation due to hepatocellular carcinoma, marked increase in DY/X and HMW fragments and slight increase in DD fragment were observed on the day of operation. Hyperfibrinolysis documented in case 4 was explained by both increased production of thrombin and moderately accelerated activation of plasmin. Both qualitative and quantitative changes in the fragments of FDP during the courses of treatment in two cases of DIC were also noted. In summary, each underlying disease expresses characteristic pattern of FDP fragments in DIC.     

Clinical significance of a new fibrinogen/fibrin degradation products(FDP) test using plasma samples for the diagnosis of fibrinogenolysis and fibrinolysis

Recently, a new fibrinogen/fibrin degradation products(FDP) test using monoclonal antibodies against FDP(LPIA FDP-P: FDP-P) has been developed, which is able to measure FDP directly in plasma. The objective of this study is to clarify clinical significance of the test in the diagnosis of fibrinogenolysis and fibrinolysis in comparison with a conventional FDP test using polyclonal antibodies against fibrinogen(FDP-S) and D-dimer test using monoclonal antibodies against D-dimer(D-D). The monoclonal antibodies used in FDP-P test was shown to recognize fragment X, Y and D1 derived from fibrinogen digested by urokinase, and was also to recognize XDP fragments, D-dimer and D derived from cross-linked fibrin digested by tissue plasminogen activator using SDS-PAGE and immunoblotting analysis. There was a good correlation of FDP levels between FDP-P test and FDP-S test. However, levels of FDP in both tests were discrepant in several samples. There was a tendency that the levels of FDP were higher in FDP-S test than in FDP-P test. Such discrepancy was suggesting that soluble fibrin monomer complex(FM) was recognized by the antibodies used in FDP-S test, but not recognized by the antibodies used in FDP-P test. There was also a good correlation of FDP levels between FDP-P test and D-D test. However, the levels of FDP in both tests were discrepant in several samples. The levels of FDP were higher in FDP-P test than in D-D test. These discrepant samples had lower levels of antiplasmin and higher levels of plasmin antiplasmin complex(PIC), and also showed XDP fragments, D-dimer, X, Y, and D1 by using SDS-PAGE. These observations suggest that D-D test measures only fibrinolytic fragments, while FDP-P test measures fibrinogenolytic fragments as well as fibrinolysis. In results, the FDP-P test was confirmed to be a useful tool to examine fibrinogenolysis as well as fibrinolysis more specifically than the conventional FDP test.     

Analysis of cross-linked fibrin and fibrinogen degradation products with SDS-PAGE and immunoblot

SDS-PAGE and immunoblot technique with anti-FDP-D, -FDP-E, -fibrinogen antibody or anti-FDP-DD monoclonal antibody were applied to analyze FDP fragments prepared from cross-linked fibrin and fibrinogen with plasmic digestion in vitro. FDP fragments of DY(260K), DD(187K), X(245K), Y(166K), D(77K, 97K), E1(58K), E2(46K) and E3(40K) were identified from data of molecular weight and reactivity to four antibodies referred to reports of other investigators. Serum FDP fragments from five DIC suspected patients were analyzed by the same methods. In two patients' sera, DD fragment was a main component, and in the other three patients' sera, D fragment was a main fraction. Proportions of high molecular weight fragments of FDP were considerably different in patients' sera. Appearance of D fragment in our cases was considered to be derived from unstable fibrin (fibrin monomer and dimer) rather than from fibrinogen. Molecular weight of DD fragments from patients' sera had heterogeneity (160 approximately 180K), and the values were different from that (187K) prepared from cross-linked fibrin. In conclusion, SDS-PAGE and immunoblot analysis of serum fragments of FDP will be an useful technique to investigate the clinical and pathological condition of DIC.     

Measurement of plasma fibrin D-dimer levels with the use of a monoclonal antibody coupled to latex beads

Recently, monoclonal antibody (DD-3B6) to fibrin D-dimer was prepared and coupled to latex beads to provide a specific test (Dimertest) for fibrinolysis. The purpose of this study was to evaluate the Dimertest assay as a clinical laboratory test for the measurement of plasma fibrin D-dimer derivatives. The Dimer-test assay specifically detected 2 micrograms/mL of purified fibrin D-dimer or fibrin D-dimer/fragment E complex added to afibrinogenemic plasma but did not detect 500 micrograms/mL of either fibrinogen fragments X, D, E, or 160 micrograms/mL cross-linked fibrinogen. The fibrin(ogen) degradation product (FDP) assays of American Dade or Wellcome Diagnostics detected 5.0 micrograms/mL of fibrin D-dimer and from 1 to 10 micrograms/mL of the other FDPs. Twenty-eight percent of 150 random plasma samples assayed from hospitalized patients were positive for fibrin D-dimer derivatives. Plasma samples from 152 patients suspected of having disseminated intravascular coagulation (DIC) were assayed for serum FDP (Wellcome Diagnostics) and plasma fibrin D-dimer derivatives. Samples from 69% of patients with serum FDP levels less than 10 micrograms/mL, and more than 90% of those with serum FDP levels greater than 10 micrograms/mL, were positive for fibrin D-dimer derivatives. Dimertest results were not modified by heparin, streptokinase, freeze-thawing, or clotting plasma. Serum fibrinogen-related antigens were immunoadsorbed from Dimer-test positive sera by anti-fibrinogen antibody and formalin-fixed Cowan I strain Staphylococcus aureus. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and protein blotting with the use of monoclonal antibody DD-3B6 demonstrated a protein band with similar mobility to purified D-dimer. The measurement of plasma fibrin D-dimer derivatives by the Dimertest assay is a rapid, sensitive, and specific laboratory test for fibrinolysis. The Dimertest assay has proven to be a useful addition to the clinical laboratory and should be helpful in the diagnosis and management of patients with diseases associated with fibrinolysis.     

Incidence and possible reasons for discordant results between positive FDP and negative D-dimer latex assays in clinical specimens.

In general, FDP and D-dimer values have a correlation in clinical conditions associated with disseminated intravascular coagulation(DIC) or coagulation activation. However, there are some patients with discordant results who demonstrate elevated FDP and negative D-dimer results by latex agglutination assays. The incidence and possible reasons for the discordance between FDP and D-dimer results were investigated through simultaneous measurements (n = 763) from clinical patients with suspected DIC or coagulation activation. 24.8% (189/763) of samples with elevated FDP were negative for D-dimer assays by the latex agglutination method. Further detailed analysis on randomly-selected discordant samples (n = 41) revealed that the most common reason for the discordance was the lower sensitivity of the semiquantitative latex agglutination method for D-dimer, compared with quantitative enzyme or other latex immunoassay. The other contributing factors to the discordance were accelerated fibrinogenolysis without secondary fibrinolysis, elevated soluble fibrin monomer and rheumatoid factor.     

Interpretation of hemostatic and fibrinolytic markers

Blood dose not normally coagulate in the blood vessels covered with endothelial cells, because these cells contain some substances responsible for antithrombotic action such as thrombomodulin, heparin-like substance, prostacyclin, nitric oxide and tissue plasminogen activator. Most important role of blood coagulation is hemostasis. Blood can coagulate in two ways: intrinsic coagulation pathway and extrinsic coagulation pathway that is activated by negatively charged substances and FVIIa-tissue-factor (TF) complex, respectively. Prothrombin time(PT) can represent extrinsic pathway, while activated partial thromboplastin time (APTT) can represent intrinsic pathway. PT is prolonged in such diseases as vitamin K deficiency, hepatic failure and warfarin intake, while APTT is prolonged such diseases as hemophilia A & B, von Willebrand disease and lupus anticoagulant. Cross mixing test is very useful to assess prolonged clotting time. FDP means fibrin/fibrinogen degradation products and D-dimer is the smallest products of fibrin degradation. These markers are often used to diagnose disseminated intravascular coagulation (DIC) and deep vein thrombosis (DVT). Thrombin-antithrombin complex (TAT) and plasmin-alpha2 plasmin inhibitor (PIC) can be used to evaluate the extent of coagulation and fibrinolysis activation, respectively. These two markers is essential for classify the pathophysiology of DIC: DIC with suppressed fibrinolysis, enhanced fibrinolysis or balanced fibrinolysis. In conclusion, exact interpretation of hemostatic and fibrinolytic markers is one of the most important abilities in clinical situation.     

A case of hookworm infestation with dissociation values between FDP-E and FDP-D dimer

We previously reported a five-year-old girl showing bleeding tendency and transient morphological and functional platelet abnormalities probably due to a hookworm, Necator Americanus, infestation. In this report, we describe the rarely accelerated fibrinogenolysis and/or fibrinolysis in this patient whose value of fibrinogen and/or fibrin degradation products(FDP) determined with an FDP-E assay was much higher than that determined with a D-dimer assay. Namely, on day-1 and day-13 of hospitalization, her D-dimer values were only 10 to 20% of the prospected values from FDP-E values. We speculated this phenomenon was induced by circulating protease(-like) agent(s) produced by hookworm, because the only slightly participation of plasmin and/or granulocyte elastase was evaluated by the determination of enzyme-inhibitor complexes. And the other possibility of fibrinogen degradation by blast- or tumor-associated protease was excluded by the clinical manifestations and primary disorders. In conclusion, we report a very rare case with the accelerated fibrinogenolysis and/or fibrinolysis in a patient with the hookworm infestation. We are interested in the mechanism that manifested the patient's bleeding tendency accompanied with morphological and functional platelet abnormalities.     

Pharmacokinetics of degradation products of fibrin and fibrinogen during alteplase therapy of acute myocardial infarction

Pharmacokinetics of fibrin degradation products (FbDP), D-dimers, fibrinogen degradation products (FgDP) and total degradation products (TDP) in plasma were investigated using ELISA methods in 12 patients undergoing therapy with alteplase (100 mg/3 h) for acute myocardial infarction. Peak concentrations of all degradation products occurred significantly later (1.6–2.5 h) than peak alteplase levels (2 min). Peak D-dimer concentrations (mean 2.6 μg/ml) were significantly lower than those of FbDP (7.1 μg/ml) or FgDP (7.8 μg/ml). However, the half-life of D-dimers (mean 13.3 h) was more than 4.5-fold longer than that of FbDP (2.9 h) or FgDP (2.8 h) (p<0.001). Consequently, areas under the plasma concentration-time curve (AUC) of D-dimers were comparable with those of FbDP or FgDP The ratios AUC(FbDP)/AUC(FgDP) and AUC(D-dimers)/AUC(FgDP) are proposed as new indices of fibrin specificity. Their values in this study (geometric mean, 95% CI) were 1.15 (0.60–2.20) and 1.30 (0.52–3.24) respectively. It is concluded that cross-linking may prolong the half-life of fibrin degradation products, and that complete time profiles of fibrin- and fibrinogen degradation products in plasma, rather than single point measurements, are essential for reliable quantification of fibrin specificity.     

Fibrinogen and fibrinogen/fibrin degradation products in the urine of rabbits infected with Trypanosoma (Trypanozoon) brucei

Summary Studies have been carried out on the urine of rabbits infected with Trypanosoma (Trypanozoon) brucei to determine whether fibrinogen or fibrinogen/fibrin degradation products (FDP) could be detected. No fibrinogen was found but during the last two weeks of this 7-week infection low levels of FDP were present in the urine which did not exceed 5 g/ml. Rabbit urine was shown to contain a potent proteolytic enzyme capable of breaking down rabbit fibrinogen and both early and late FDP were present in the cleavage products. No deposits of fibrin were detected in the kidney, but casts were present in the urine suggesting renal damage. The most likely explanation of the urinary FDP is that either an increase in the glomerular permeability occurs allowing filtration of plasma FDP or a local fibrinogenolysis in the kidney tubules.     

Diagnosis of disseminated intravascular coagulation. Role of D-dimer

Detection of the cross-linked fibrin degradation fragment, D-dimer, in patients at risk for disseminated intravascular coagulation (DIC) is strong evidence for the diagnosis. D-dimer confirms that both thrombin generation and plasmin generation have occurred. Patients at risk for DIC (58) and normal controls (7) were studied. Thirty-three patients had DIC--with fragment D-dimer identified in their serum by immunoblotting. Latex agglutination measurements of fibrin(ogen) degradation products (FDPs) and D-dimer were compared with immunoblotting in the detection of D-dimer. FDP measurement was extremely sensitive but not specific. D-dimer measurement was less sensitive but highly specific. Used in tandem, screening with FDP and confirming with D-dimer, sensitivity and specificity were maximized, rendering a predictive value of a confirmed FDP of 100% in this cohort. D-dimer is a valuable adjunct for the laboratory diagnosis of DIC but is most appropriately used as a confirmatory test for the very sensitive FDP test.     

Criteria for diagnosing DIC

The differences between reagents of prothrombin time (PT), fibrinogen and fibrin and fibrinogen degradation products(FDP) were examined in patients with disseminated intravascular coagulation (DIC) and without DIC. The sensitivity of the PT ratio for DIC is lowered by the PT reagent with a high international sensitivity index, and the difference between PT reagents was marked. The sensitivity of PT-international normalized ratio (INR) for DIC was higher than that of the PT ratio and the difference between reagents in PT-INR was low. Though the difference between reagents for fibrinogen is slight, the usefulness in diagnosing DIC is also slight. Though the sensitivity of FDP for DIC was good, the difference between FDP reagents was marked. Therefore, standardization of PT and FDP seems to be necessary. Concordance of overt-DIC diagnostic criteria by the International Society of Thrombosis and Haemostasis (ISTH) and DIC diagnostic criteria of Japanese Ministry of Health and Welfare (JMHW) was about 70%, and overt-DIC diagnostic criteria of ISTH seemed to diagnose the typical type of DIC diagnosed by JMHW criteria. Finally, the diagnostic criteria of non-overt DIC are expected to become increasingly important.     

An immunohistochemical study of experimental disseminated intravascular coagulation (DIC)

The experiment was focused on clarifying changes in fibrin or fibrinogen related materials (FRMs) in blood, urine, and renal tissues of rats with disseminated intravascular coagulation (DIC). DIC was induced by a continuous infusion of massive volume of physiologic saline (100 ml) immediately after endotoxin injection. FRM response was checked by biochemical and histochemical examinations at various intervals. In the blood of DIC rats, platelet and fibrinogen levels initially decreased, followed by an increasing plasma fibrin degradation products (FDP). Parallel with elevation of blood FDP the percentage of glomeruli with FRMs increased. Thereafter, FRMs were observed in renal tubuli and urine. Our observations indicated that FRMs in renal tubuli were derived from glomerular capillaries via Bowman's space. In conclusion, in DIC the immunoenzymehistochemical (IEH) procedure appeared necessary for an accurate pathological diagnosis, and the presence of FRMs in renal tubuli appeared to be an important finding even in absence of FRMs in glomeruli.     

AN IMMUNOHISTOCHEMICAL STUDY OF EXPERIMENTAL DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

The experiment was focused on clarifying changes in fibrin or fibrinogen related materials (FRMs) in blood, urine, and renal tissues of rats with disseminated intravascular coagulation (DIC). DIC was induced by a continuous infusion of massive volume of physiologic saline (100 ml) immediately after endotoxin injection. FRM response was checked by biochemical and histo-chemical examinations at various intervals. In the blood of DIC rats, platelet and fibrinogen levels initially decreased, followed by an increasing plasma fibrin degradation products (FDP). Parallel with elevation of blood FDP the percentage of glomeruli with FRMs increased. Thereafter, FRMs were observed in renal tubuli and urine. Our observations indicated that FRMs in renal tubuli were derived from glomerular capillaries via Bowman's space. In conclusion, in DIC the immunoenzymehistochemical (IEH) procedure appeared necessary for an accurate pathological diagnosis, and the presence of FRMs in renal tubuli appeared to be an important finding even in absence of FRMs in glomeruli.     

Degradation products of fibrin and of fibrinogen in synovial fluid and in plasma of patients with rheumatoid arthritis

Degradation products of fibrin and of fibrinogen, together (FDP) and separately, were measured in plasma and synovial fluid of patients with rheumatoid arthritis using specific enzyme immunoassays. Considerable amounts of fibrin degradation products (fibrin-DP) were found in the synovial fluid; only 1 case yielded some fibrinogen-derived products (fibrinogen-DP). In plasma relatively small amounts of degradation products, both fibrin-DP and fibrinogen-DP, were present. From the discrepancy between the amount and composition of degradation products in synovial fluid and in plasma we conclude that there are extra-articular sites of fibrin(ogen) breakdown in rheumatoid arthritis. The new specific methods may contribute to the understanding of the role of fibrinolysis in rheumatoid disease and in inflammation in general.     

Prevalence and clinical implications of heparin-associated false positive tests for serum fibrin(ogen) degradation products

An electrophoretic method has been applied to characterize specific fibrinogen and fibrin degradation products (FDP) in 135 serum samples from 59 consecutive patients having a positive latex agglutination test for serum FDP in the evaluation of consumption coagulopathy. In 20 of 135 positive samples, the principal fibrinogen derivatives present were not degradation products of fibrinogen or fibrin but were instead residual fibrinogen or fibrin monomer and polymers (FFMP) due to incomplete clotting. Heparin exposure was common in patients with positive FDP tests occurring in 29 of 59 patients (49%) with 81 of 135 samples (60%). Heparin exposure by parenteral administration or catheter was significantly correlated with a false positive serum FDP test because of residual FFMP occurring in 19 of 81 (23%) samples from heparin-exposed patients but in only 1 of 54 (2%) samples from patients without exposure (P less than 0.005). Treatment of the false positive samples with reptilase, an enzyme unaffected by heparin, resulted in complete removal of the residual FFMP, and in vitro experiments demonstrated that heparin-containing plasma samples could be completely clotted with either reptilase or protamine sulfate plus thrombin. Survey of 20 regional laboratories showed that only 10% used reptilase or protamine sulfate to prepare serum if heparin exposure had occurred and that this was done in only 22 of 5,049 (0.4%) of samples in the last calendar year. Greater attention should be given to proper preparation of serum from heparin-exposed patients, and physicians should be aware of the possibility of falsely positive or falsely elevated serum FDP tests in evaluation of consumption coagulopathy in heparin-exposed patients.     

The detection of fibrinogen/fibrin degradation products by means of a new antibody-coated latex particle

A rapid slide test for the detection of degradation products of fibrinogen/fibrin (FDP) using a new antibody-coated latex particle is described. The latex particle has been specifically coated with antibody to fragments D and E. The latex agglutination test (Thrombo-Wellcotest) has been compared with the tanned red cell haemagglutination inhibition immunoassay (TRCHII) in 143 patients with a variety of clinical conditions. There is a high degree of agreement between the methods with a coefficient of correlation of 0.83. The method provides a rapid, simple screening test for fibrin degradation products.     

Clinical application of laboratory diagnosis: leukemia and DIC]

Plasma levels of molecular markers of hemostatic activation were investigated in 205 samples from patients with haematopoietic malignancies. These markers included thrombin/antithrombin III complex (TAT), D-dimer, plasmin/alpha 2plasmin inhibitor complex (PIC) and thrombomodulin (TM), and were assayed by EIA methods. Samples were divided into 4 groups according to the level of FDP: group A; FDP 10 greater than, group B; 10 less than or equal to less than 20 group C; 20 less than or equal to less than 40, and group D; less than 40. The mean level of each marker except TM increased in the order of group A, B, C and D. However, in many samples belonging to group A the plasma TAT or PIC levels and both were increased in spite of low FDP level. Furthermore, levels of TAT and PIC in several samples belonging to groups C and D were within the normal range. Also, the mean levels of each marker except TM increased in the order of 2, 3, 4, 5 and over 6 points in DIC score according to the criteria of DIC diagnosis by the research committee on DIC of the Ministry of Health and Welfare in Japan. Eight of the 11 samples (72.7%) obtained from cases with a DIC score of 3 points had high plasma levels of TAT, PIC and D-dimer. Plasma levels of these markers were increased after chemotherapy. These findings lead to the following conclusions: 1) FDP reflexed activation of coagulation and fibrinolysis, but 2) FDP was not more sensitive than TAT and PIC, and 3) the increase of FDP rarely resulted from fibrinogenolysis or non-plasmin mediated fibrinolysis. Furthermore, 4) TAT, D-dimer and PIC may serve as sensitive parameters of hemostatic activation in circulating blood and be valuable markers for early diagnosis of DIC.     

红花注射液对脂多糖诱导的兔弥散性血管内凝血的作用

 目的：研究红花注射液对脂多糖（LPS）诱导的兔弥散性血管内凝血（DIC）的作用。方法：兔耳缘静脉持续滴注LPS建立兔DIC模型。采用全自动凝血分析仪检测活化部分凝血活酶时间（APTT）和凝血酶原时间（PT）;凝固法测定纤维蛋白原含量;全自动血细胞分析仪进行血小板计数;发色底物法测定蛋白C及抗凝血酶Ⅲ的活性;全自动血浆分析仪测定丙氨酸氨基转移酶（ALT）和血尿素氮（BUN）;ELISA法检测血浆纤维蛋白（原）降解产物（FDP）和肿瘤坏死因子 α（TNF-α）含量。结果：DIC模型组APTT和PT进行性延长,ALT活性和BUN含量显著升高,蛋白C和抗凝血酶Ⅲ的活性显著降低,血小板计数进行性减少,血浆FDP和TNF-α含量显著升高。给予红花注射液后,DIC模型兔APTT和PT的延长明显缩短,血小板计数、纤维蛋白原含量、蛋白C及抗凝血酶Ⅲ活性均明显恢复,血浆ALT、BUN、FDP和TNF-α水平均明显降低。结论: 红花注射液对LPS诱导的兔DIC有较好的拮抗作用。     

Clinical evaluation of a test for plasma fibrin/fibrinogen degradation products (FDP) based on monoclonal anti-FDP antibody technology: an application for the scoring system of the disseminated intravascular coagulation (DIC) diagnostic criteria

Fibrin/fibrinogen degradation products(FDP) have been measured using serum samples which were specially prepared for the FDP test because of the usage of anti-human fibrinogen antibody for the assay. Since diagnostic criteria for DIC were established by the study group on thrombosis and hemostasis which is supported by the Japanese Ministry of Health and Welfare(JMHW), serum FDP assay have been used as standard methods to diagnose DIC in Japan. Recently, a reagent using an anti-human FDP monoclonal antibody was developed and this has enabled the use of plasma samples for FDP measurement. The comparability, especially of the DIC score, of a new assay, Latex test BL-2 P-FDP, using plasma samples with a conventional assay for serum was investigated. Two sets of DIC scores based on data from the two tests were compared and the correlation was high with 97.5% of the patients being diagnosed with the same DIC status. In four disease groups--DIC, thrombosis, leukemia and solid cancer--high comparability between the two tests was also shown and no significant difference was observed in the correlation coefficient and the slope coefficient between serum and plasma samples. To conclude, it is suggested that "Latex test BL-2 P-FDP" is applicable to the diagnostic criteria for DIC from JMHW without any difficulty.